Trifluoromethylpropanamide derivatives as HTRA1 inhibitors

Abstract

The invention provides novel compounds having the general formula (I) wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, A and R 11 are as described herein, compositions including the compounds and methods of using the compounds.

The invention claimed is: 
     
       1. A compound of formula (I) 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts thereof, wherein 
         R 2 , R 3 , R 4 , R 5  and R 7  are each independently selected from 
         i) H, 
         ii) C 1-6 -alkyl, and 
         iii) C 3-8 -cycloalkyl; 
         X is selected from 
         i) —O—, 
         ii) —S—, and 
         iii) —S(O) 2 —; 
         R 6  is selected from 
         i) aryl substituted with at least one of R 12 , R 13  and R 14 , 
         ii) aryl-C 1-6 -alkyl substituted with at least one of R 12 , R 13  and R 14 , 
         iii) heteroaryl substituted with at least one of R 12 , R 13  and R 14 , and 
         iv) heteroaryl-C 1-6 -alkyl substituted with at least one of R 12 , R 13  and R 14 ; 
         A is selected from 
         i) —O—, 
         ii) —CH 2 —, 
         iii) —S(O) 2 NR 10 —, and 
         iv) —C(O)NR 10 —; 
         R 8  is selected from 
         i) H, and 
         ii) —CH 2 R 9 ; 
         R 9  is selected from 
         i) H, 
         ii) hydroxy, 
         iii) amino-C 1-6 -alkyl substituted on the nitrogen atom by one or two substituents selected from H, C 1-6 -alkylcarbonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R 15 , R 16  and R 17 , 
         iv) aminocarbonyl substituted on the nitrogen atom by one or two substituents selected from H, C 1-6 -alkylcarbonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R 15 , R 16  and R 17 , 
         v) aminocarbonyl-C 1-6 -alkyl substituted on the nitrogen atom by one or two substituents selected from H, C 1-6 -alkylcarbonyl, C 1-6 -alkoxycarbonyl, C 1-6 -alkyl, arylcarbonyl and heteroarylcarbonyl, wherein arylcarbonyl and heteroarylcarbonyl are substituted with at least one of R 15 , R 16  and R 17 , 
         vi) carboxy, 
         vii) carboxy-C 1-6 -alkyl, 
         viii) C 1-6 -alkoxy, 
         ix) C 1-6 -haloalkoxy, 
         x) C 1-6 -alkoxycarbonyl, 
         xi) C 1-6 -alkoxycarbonyl-C 1-6 -alkyl, 
         xii) C 3-8 -cycloalkyl, 
         xiii) aryl substituted with at least one of R 15 , R 16  and R 17 , 
         xiv) aryl-C 1-6 -alkyl substituted with at least one of R 15 , R 16  and R 17 , 
         xv) aryl-C 1-6 -alkoxy substituted with at least one of R 15 , R 16  and R 17 , 
         xvi) heteroaryl substituted with at least one of R 15 , R 16  and R 17 , 
         xvii) heteroaryl-C 1-6 -alkyl substituted with at least one of R 15 , R 16  and R 17 , and 
         xviii) heteroaryl-C 1-6 -alkoxy substituted with at least one of R 15 , R 16  and R 17    
         xix) heterocycloalkyl substituted with at least one of R 15 , R 16  and R 17 , 
         xx) heterocycloalkyl-C 1-6 -alkyl substituted with at least one of R 15 , R 16  and R 17 , 
         xxi) heterocycloalkyl-C 1-6 -alkoxy substituted with at least one of R 15 , R 16  and R 17 , and 
         xxii) C 1-6 -alkylsilyloxy; 
         R 10  is H; 
         R 11  is selected from 
         i) amino-C 1-6 -alkyl substituted on the nitrogen atom by at least one of R 21  and R 22 , 
         ii) C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         iii) C 3-8 -cycloalkyl-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         iv) C 3-8 -cycloalkyl(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         v) aryl substituted with at least one of R 18 , R 19  and R 20 , 
         vi) aryl-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         vii) aryl-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         viii) aryl-heterocycloalkyl substituted with at least one of R 18 , R 19  and R 20    
         ix) aryl(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         x) aryl(halo)-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xi) aryl(halo)-heterocycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xii) aryloxy-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xiii) aryloxy-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xiv) aryloxy-heterocycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xv) aryloxy(halo)-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xvi) aryloxy(halo)-heterocycloalkyl substituted with at least one of R 18 , R 19  and R 20    
         xvii) aryloxy(halo)-C 1-6 -alkyl, 
         xviii) heterocycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xix) heterocycloalkyl-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xx) heterocycloalkyl-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         xxi) heterocycloalkyl(halo)-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         i) heterocycloalkyl(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         ii) heteroaryl substituted with at least one of R 18 , R 19  and R 20 , 
         iii) heteroaryl-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         iv) heteroaryl-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         v) heteroaryl(halo)-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         vi) heteroaryl(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         vii) heteroaryloxy-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , 
         viii) heteroaryloxy-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
         ix) heteroaryloxy(halo)-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , and 
         x) heteroaryloxy(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 ; 
         R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19  and R 20  are each independently selected from 
         i) H, 
         ii) cyano, 
         iii) halogen, 
         iv) oxo, 
         v) C 1-6 -alkyl, 
         vi) amino substituted on the nitrogen atom by two substituents independently selected from H, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl, arylcarbonyl and heteroarylcarbonyl, 
         vii) amino-C 1-6 -alkyl substituted on the nitrogen atom by two substituents independently selected from H, C 1-6 -alkyl, C 1-6 -alkoxycarbonyl, arylcarbonyl and heteroaryl carbonyl, 
         viii) C 1-6 -alkyl, 
         ix) halo-C 1-6 -alkyl, 
         x) C 3-8 -cycloalkyl, 
         xi) C 1-6 -alkoxycarbonyl-C 1-6 -alkyl, 
         xii) carboxy-C 1-6 -alkyl, 
         xiii) C 1-6 -alkoxycarbonyl-C 1-6 alkylaminocarbonyl-C 1-6 alkyl, 
         xiv) carboxy-C 1-6 -alkylaminocarbonyl-C 1-6 alkyl, 
         xv) C 1-6 -alkoxy, 
         xvi) halo-C 1-6 -alkoxy, 
         xvii) C 1-6 -alkoxycarbonyl-C 1-6 -alkoxy, 
         xviii) carboxy-C 1-6 -alkoxy, 
         xix) C 1-6 -alkoxycarbonyl-C 1-6 -alkylaminocarbonyl-C 1-6 -alkoxy, 
         xx) carboxy-C 1-6 -alkylaminocarbonyl-C 1-6 -alkoxy, and 
         xxi) heterocycloalkyl; 
         and 
         R 21  and R 22  are each independently selected from 
         i) H, 
         ii) C 1-6 -alkoxycarbonyl, 
         iii) carboxy-C 1-6 -alkyl, 
         iv) arylcarbonyl, and 
         v) heteroarylcarbonyl; 
         with the proviso that N-[(1S)-1-[[(1S)-1-[(2S,4R)-4-benzyloxy-2-[(1-ethyl-3,3,3-trifluoro-2-oxo-propyl)carbamoyl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamoyl]-2-methyl-propyl]pyrazine-2-carboxamide is excluded. 
       
     
     
       2. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 R 2  is C 1-6 -alkyl; 
 R 3 , R 4 , R 5  and R 7  are each H; 
 X is selected from 
 i) —O—, 
 ii) —S—, and 
 iii) —S(O) 2 —; 
 R 6  is phenyl-C 1-6 -alkyl substituted with at least one of R 12 , R 13  and R 14 ; 
 A is selected from 
 i) —O—, 
 ii) —CH 2 —, 
 iii) —S(O) 2 NR 10 — and 
 iv) —C(O)NR 10 —; 
 R 8  is selected from 
 i) H, and 
 ii) —CH 2 R 9 ; 
 R 9  is selected from 
 i) H, 
 ii) hydroxy, 
 iii) C 1-6 -alkoxy, 
 iv) phenyl substituted with at least one of R 15 , R 16  and R 17 , and 
 v) C 1-6 -alkylsilyloxy; 
 R 11  is selected from 
 i) phenyl substituted with at least one of R 18 , R 19  and R 20 , 
 ii) phenyl-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
 iii) phenyl(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , and 
 iv) heteroaryl substituted with at least one of R 18 , R 19  and R 20 , wherein heteroaryl is selected from
 a. pyrazinyl, 
 b. pyridinyl, and 
 c. thiophenyl; 
 
 R 12  is selected from 
 i) H, and 
 ii) C 1-6 -alkoxy, 
 R 15  is selected from 
 i) H, 
 ii) halogen, and 
 iii) amino-C 1-6 -alkyl substituted on the nitrogen atom by one H and one C 1-6 -alkoxycarbonyl; 
 R 18  is selected from 
 i) H, 
 ii) halogen, and 
 iii) halo-C 1-6 -alkyl; 
 and 
 R 13 , R 14 , R 16 , R 17 , R 19  and R 20  are each H; 
 with the proviso that N-[(1S)-1-[[(1S)-1-[(2S,4R)-4-benzyloxy-2-[(1-ethyl-3,3,3-trifluoro-2-oxo-propyl)carbamoyl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamoyl]-2-methyl-propyl]pyrazine-2-carboxamide is excluded. 
 
     
     
       3. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2  is C 1-6 -alkyl. 
     
     
       4. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 , R 4 , R 5  and R 7  are each H. 
     
     
       5. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is selected from
 i) —O—, and 
 ii) —S(O) 2 —. 
 
     
     
       6. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is —O—. 
     
     
       7. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 6  is phenyl-C 1-6 -alkyl substituted with at least one of R 12 , R 13  and R 14 . 
     
     
       8. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is selected from
 i) —O—, and 
 ii) —CH 2 —. 
 
     
     
       9. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is —O—. 
     
     
       10. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 8  is H. 
     
     
       11. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9  is selected from
 i) H, 
 ii) hydroxy, 
 iii) C 1-6 -alkoxy, 
 iv) phenyl substituted with at least one of R 15 , R 16  and R 17 , and 
 v) C 1-6 -alkylsilyloxy. 
 
     
     
       12. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9  is phenyl substituted with at least one of R 5 , R 16  and R 17 . 
     
     
       13. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11  is selected from
 i) phenyl substituted with at least one of R 18 , R 19  and R 20 , 
 ii) phenyl-C 3-8 -cycloalkyl substituted with at least one of R 18 , R 19  and R 20 , 
 iii) phenyl(halo)-C 1-6 -alkyl substituted with at least one of R 18 , R 19  and R 20 , and 
 iv) heteroaryl substituted with at least one of R 18 , R 19  and R 20 , wherein heteroaryl is selected from
 (a) pyrazinyl, 
 (b) pyridinyl, and 
 (c) thiophenyl. 
 
 
     
     
       14. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11  is phenyl substituted with at least one of R 18 , R 19  and R 20 . 
     
     
       15. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 12  is selected from
 i) H, and 
 ii) C 1-6 -alkoxy. 
 
     
     
       16. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 12  is H. 
     
     
       17. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 15  is selected from
 i) H, 
 ii) halogen, and 
 iii) amino-C 1-6 -alkyl substituted on the nitrogen atom by one H and one C 1-6 -alkoxycarbonyl. 
 
     
     
       18. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 15  is H. 
     
     
       19. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 18  is selected from
 i) H, 
 ii) halogen, and 
 iii) halo-C 1-6 -alkyl. 
 
     
     
       20. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 18  is halogen. 
     
     
       21. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 13 , R 14 , R 16 , R 17 , R 19  and R 20  are each H. 
     
     
       22. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein
 R 2  is C 1-6 -alkyl; 
 R 3 , R 4 , R 5  and R 7  are each H; 
 X is —O—; 
 R 6  is phenyl-C 1-6 -alkyl substituted with at least one of R 12 , R 13  and R 14 ; 
 A is —O—; 
 R 8  is H; 
 R 9  is phenyl substituted with at least one of R 15 , R 16  and R 17 ; 
 R 11  is phenyl substituted with at least one of R 18 , R 19  and R 20 ; 
 R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 19  and R 20  are each H; and 
 R 18  is halogen. 
 
     
     
       23. A compound according to  claim 1 , selected from the group consisting of:
 N-((S)-3-(3-chlorophenyl)-1-((2S,4R)-4-((4-methoxybenzyl)sulfonyl)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)picolinamide; 
 N-((S)-3-(3-chlorophenyl)-1-((2S,4R)-4-((4-methoxybenzyl)sulfonyl)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-1-oxopropan-2-yl)pyrazine-2-carboxamide; 
 (2S,4R)-1-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide; 
 (2S,4R)-1-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide; 
 (2S,4R)-1-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-methoxypropanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide; 
 (2S,4R)-1-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-3-methoxypropanoyl]-4-[(4-methoxyphenyl)methylsulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide; 
 tert-butyl N-[[4-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methyl sulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate; 
 tert-butyl N-[[4-[(2S)-2-[(3-chlorobenzoyl)amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methyl sulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate; 
 tert-butyl N-[[4-[(2S)-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methylsulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate; 
 tert-butyl N-[[4-[(2S)-2-[[1-(4-chlorophenyl)cyclopentanecarbonyl]amino]-3-[(2S,4R)-4-[(4-methoxyphenyl)methyl sulfonyl]-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]carbamoyl]pyrrolidin-1-yl]-3-oxopropyl]phenyl]methyl]carbamate; 
 (2S,4R)-1-(2-(3,5-dichlorophenoxy)acetyl)-4-((4-methoxybenzyl)sulfonyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 (2S,4R)-1-(2-(3,5-dichlorophenoxy)acetyl)-4-((4-methoxybenzyl)thio)-N-((R)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 (2S,4R)-4-(benzyloxy)-1-(3-(3,4-dichlorophenyl)propanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 (2S,4R)-4-(benzyloxy)-1-(2-(3,5-dichlorophenoxy)acetyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 N-((S)-1-((2S,4R)-4-(benzyloxy)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-3-(3-chlorophenyl)-1-oxopropan-2-yl)picolinamide; 
 N-((S)-1-((2S,4R)-4-(benzyloxy)-2-(((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl)pyrrolidin-1-yl)-3-(3-chlorophenyl)-1-oxopropan-2-yl)pyrazine-2-carboxamide; 
 (2S,4R)-4-(benzyloxy)-1-((R)-2-(3,5-dichlorophenoxy)-3-phenylpropanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 (2S,4R)-1-[(2S)-2-[(5-chlorothiophen-2-yl)sulfonylamino]-3-methoxypropanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide; 
 (2S,4R)-1-[(2S)-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]-3-hydroxypropanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide; 
 (2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[[2-(3-chlorophenyl)-2,2-difluoroacetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methylsulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid; 
 (2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[(3-chlorobenzoyl)amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid; 
 (2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[[2,2-difluoro-2-[2-(trifluoromethyl)phenyl]acetyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid; and 
 (2S,4R)-1-[(2S)-3-[4-(aminomethyl)phenyl]-2-[[1-(4-chlorophenyl)cyclopentanecarbonyl]amino]propanoyl]-4-[(4-methoxyphenyl)methyl sulfonyl]-N-[(3S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl]pyrrolidine-2-carboxamide;2,2,2-trifluoroacetic acid; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       24. The compound of  claim 1 , selected from the group consisting of:
 (2S,4R)-1-(2-(3,5-dichlorophenoxy)acetyl)-4-((4-methoxybenzyl)sulfonyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 (2S,4R)-4-(benzyloxy)-1-(3-(3,4-dichlorophenyl)propanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 (2S,4R)-4-(benzyloxy)-1-(2-(3,5-dichlorophenoxy)acetyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; and 
 (2S,4R)-4-(benzyloxy)-1-((R)-2-(3,5-dichlorophenoxy)-3-phenylpropanoyl)-N-((S)-1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carboxamide; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       25. A process to prepare the compound of  claim 1  comprising the reaction of a compound of formula (II) in oxidative conditions 
       
         
           
           
               
               
           
         
       
     
     
       26. A pharmaceutical composition comprising the compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier. 
     
     
       27. A method for the treatment of an HtrA1-mediated condition selected from the group consisting of wet or dry age-related macular degeneration, geographic atrophy, diabetic retinopathy, retinopathy of prematurity and polypoidal choroidal vasculopathy, which method comprises administering to a mammal in need thereof an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
       28. The compound of  claim 1 , wherein said compound is manufactured according to a process comprising the reaction of a compound of formula (II) in oxidative conditions